21st Century CPU – The Future of Clinical Pharmacology Units and Early Phase Clinical Research

1. 21st Century CPU – The Future of Clinical Pharmacology Units and Early Phase Clinical Research A Panel Discussion 21st Annual ACPU Meeting NIH Clinical Center April 26, 2012

2. Format of Session • Introduction & Background • Panelists comments and generation of topics to discuss • What has changed, is changing, will change? • Panel Discussion on leading topics • Identify attributes of ‘ideal’ CPU • What would you build with a blank check? • Audience questions

3. “Overview of the Phase I Market” • Ken Getz, Tufts CSDD; Oct 2010 ACPU • Drug Development Landscape • Phase I Market • Market Trends • Opportunities

4. Ask the Experts • Broad perspective of expertise • Academia • Rob Califf, Carl Peck, [Stephen Spielberg] • CROs • Oren Cohen, Royce Morrison • Pharma, big & small • Matt Troyer (John Wagner), Diane Jorkasky • Regulatory • Stephen Spielberg, [Carl Peck]

5. Drug Development Landscape Commercialization Conditions • Restrictive price controls • Healthcare reform uncertainty and adverse impact • Depressed global markets • High-level of revenue at risk R&D Operating Conditions • Low success rates • Declining levels of innovation • Rapidly rising R&D costs • Regulatory conservatism • Public discontent Getz, ACPU Oct 2010

6. “Patent Cliff”

7. Downsizing of Pharma Getz, Overview of the Phase I Market, Oct 2010 ACPU Meeting

8. Declining New Drugs per R&D $ Kaitin, CP&T, 2010; 87(3):356-361

9. R&D Cost Drivers Chronic and complex indications Clinical trial size Protocol design complexity Patient recruitment/retention High cost discovery/research tools Regulatory demands Market oriented studies Late-stage attrition Getz, ACPU Oct 2010

10. Growing Protocol Complexity Getz, Overview of the Phase I Market, Oct 2010 ACPU Meeting

11. Global Phase I Facilities Getz, Overview of the Phase I Market, Oct 2010 ACPU Meeting

12. Phase I CPUs & Number of Beds Getz, Overview of the Phase I Market, Oct 2010, ACPU Annual Meeting

13. Trends in the Phase I Market • Heightened safety concerns • Emphasis on hospital and in-patient settings • Shift to US and Canada for time and cost advantages post EU-Directive • Increasing proportion of patients vs. NHV • Modified and combination protocol designs • Transfer operating risk to CROs • Growing entry by for-profit, community-based investigative sites Source: Tufts CSDD interviews

14. The Times They Are a-changin’ [“you better start swimming or you’ll sink like a stone…”] Greenberg, DIA Global Forum, Feb 2012

15. Pressures in Clinical Research • Off shoring clinical trials • Transfer operating risk to CROs & partnering with AMCs • Personalized medicine – fad or future? • Advances in genomics, proteomics, biomarkers, imaging, diseases models, bioinformatics, etc. • Regulatory and social pressures on safety for longer term studies • Public discontent with Pharma

16. Commercialization Conditions • Economic crunch on Pharma productivity • Consolidation of Pharma companies • Restrictive price controls • Healthcare reform uncertainty and its adverse impact • Depressed traditional markets & growing emerging markets • Patent cliff and revenue at risk

17. R&D Operating Conditions • Lower success rates • Declining levels of innovation • Increase in biologics and biosimilars • Rapidly rising R&D costs, and outsourcing demand • Regulatory conservatism

18. Trends in the Phase I Market • CPUs from Pharma owned and operated to CROs • Heightened safety concerns • Emphasis on hospital and in-patient settings • Shift to US and Canada for time and cost advantages post EU Directive • Increasing proportion of patients vs. NHV • Combination protocol designs, incl SAD/MAD/POC & adaptive designs • Growing role of community-based investigative sites

19. Why these Panelists? • Rob Califf: clinical research in AMC • Oren Cohen: heads phase I in leading global CRO • Diane Jorkasky: duel CPU operations and pharma • Royce Morrison: clinician, CPU PI, CRO CMO • Carl Peck: FDA CDER, drug development ‘guru’ • Stephen Spielberg: academic, pharma, now FDA • John Wagner (Matt Troyer): current sponsor view

20. Why these Panelists? Among the 7 panelists: • Over 180 years experience in clinical research in over 1000 clinical trials • Co-authored over 2000 Publications • Given over 3000 Presentations • Participated in hundreds of INDs and NDAs in various capacities

21. Thank you Let’s get going ….